The nature of the invention and its background can be determined from the discussion in the patents which are incorporated herein by reference but a short explanation may be clarifying.
The so-called automatic chemistry apparatus which has become quite useful and advantageous in being able to assay many of the tests required in modern medicine is based upon the development of many different procedures for testing blood and blood serum. The technician generally dilutes the serum and adds one or two or perhaps even three reagents in certain quantities. The resulting sample is thoroughly mixed and incubated at a particular temperature or even cooled in certain cases. After a certain amount of time depending upon the nature of the test, the sample acquires a particular color. The technician directs the beam from a photometer that produces radiation of a particular wavelength and measures the amount of the radiation which is absorbed by the sample as a measure of a chemical constituent of the serum.
There are such tests for cholesterol, glucose, protein, calcium, albumin, uric acid and many enzymes.
The advantage of the automatic chemistry apparatus is that a large number of these tests can be conducted in a short time and in the case of a large hospital or testing laboratory the volume of testing required demands some form of automation.
Two aspects of such tests provide information to the physician and the researcher. The first is the end point of the test and the second is the kinetic progress of the test. Automatic chemistry apparatus have been developed and are in use at this time to provide end points, but there have been very few devices which enable the determination of the kinetic progress of a reaction.
The patents whose disclosures are incorporated herein teach an automatic chemistry apparatus which enables kinetic measurement of many samples by multiple wavelength radiation in a highly automated and reliable manner.
The device of said patents includes a turntable with sample support members such as cuvettes that are automatically provided with aliquots of samples, the turntable rotating slowly in a stepping action. After somewhat less than a revolution, the samples are removed, the cuvettes washed and tested in this condition and other samples introduced, the procedure being a continuous one. In the meantime a rotor carrying a plurality of photometers, eight in the incorporated patents, is rotating at a speed greater than that of the turntable, continuously scanning the sample support members but obtaining readings during dwell periods of the stepping movement. Each sample support member is therefore traversed by all of the beams of radiation many times before it has made the complete circuit of one revolution and a considerable amount of data has been obtained. This data is fed into a computer which computes the desired results and a readout is obtainable from the memory of the computer. The kinetic characteristic of each sample is available in addition to end points, either as a single value representing rate or as a series of values or in a graphic display.
In the above described apparatus, it is preferred that the sample support members comprise cuvettes which are transparent and that the beams of radiation pass into the cuvettes, through the aliquot or wash water or a blank which may be in the cuvette, out of the cuvette and thence to a photocell which responds to the amount of radiation which is not absorbed by the aliquot or sample. In such cases, it is obvious that the sample must be liquid, although the patents are not necessarily limited to transparent or translucent samples in transparent cuvettes.
In U.S. Pat. No. 4,234,539 there is disclosed and claimed a type of automatic chemistry apparatus in which, instead of a rotating turntable of sample support members carrying samples, the sample support members are contained in a carrier which is fixed and does not rotate. Such a carrier could be a disposable article or could be reused. It is intended to be mounted on the apparatus manually and removed when the tests are all completed or the carrier may be fixed and the sample support members individually removed or replaced selectively. The same rotor arrangement with multiple photometers is used, rotating at a relatively rapid rate to gain data concerning the aliquots carried in the sample support members or cuvettes of the fixed carrier. In the said U.S. Pat. No. 4,234,539 the rotation rate is about ten revolutions per minute.
This invention utilizes a circular, arcuate or rectilinear array of samples which is fixed and also a rotor or moving carriage which has a plurality of photometers whose beams scan the samples multiple times for the testing procedure, but the apparatus of the invention differs in the manner in which the samples are carried, the data is gathered and in many other respects.
Specifically, the samples of the invention herein are not arranged for transmission of radiant energy fully through the sample which is preferred by the inventions of the incorporated patents. The samples are disposed in a manner such that the reaction which occurs therein is measured by reflectance. This will be described in detail hereinafter.
Recently a type of apparatus has been developed by the several different groups including Kodak Ektachem Clinical Chemistry Products division of Eastman Kodak Company which utilizes what are termed "slides" which may be about the same size as laboratory glass slides. The slides are in the nature of cartridges because they are used once and then discarded. These slides are sample-carrying members which have the necessary reagents for chemical tests already in place. The user applies a drop or so of serum, plasma or whole blood to the slide at a particular location and then measures the reaction by reflecting light from the location where the reaction is occurring, thereafter picking up the reflected light in a photocell.
The details of one embodiment of this technique are published in the following references:
"Clinical Chemistry System With No Wet Reagents", Clinical Lab Products, Volume 7, Number 10, October 1978; PA1 "Evaluation of an Engineering Model of the "EKTACHEM" Analyzer for Glucose and Urea Assay" Cate, et al, Clinical Chemistry, February 1980, p. 266 to 270; PA1 "A New Technology for the Clinical Laboratory" Przybylowicz, paper presented at American Association for Clinical Chemistry Meeting, San Francisco, California, July 23-28, 1978.
There are some important disadvantages of the apparatus which is disclosed in the above references and these relate to the amount of information which can be obtained, the throughput of samples and the complexity of the apparatus. For example, there is only one measuring position for all photometric tests as a result of which there is a very low throughput for rate reactions.
There is also a distinct disadvantage of the apparatus of the incorporated patents which utilizes a rotating turntable of cuvettes. The time for a complete revolution of the turntable is of the order of ten minutes and this means that an aliquot will remain on the turntable all that time. If the end point of the reaction has been reached some time before ten minutes have elapsed, the remaining time is wasted because the particular aliquot has to work its way around to the wash station even though the computer has already recorded the end point and may have noted that the reaction characteristic is now linear.
If liquid samples are being used with the fixed carrier of U.S. Pat. No. 4,234,539 the carrier cannot be removed from the apparatus until all tests are completed in which case any that have gone to an early end point must remain until the end of testing.
The invention herein obviates the disadantages mentioned bove.